A limiting factor associated with the use in animals, such as humans, of implantable medical devices such as heart valves, hip joints, vascular grafts, skin substitutes and implantable biosensors, is the foreign body reaction of the tissues to the materials used to fabricate the medical device. Despite decades of biomaterial research and development, these difficulties with biocompatibility hinder the life span and effectiveness of implanted medical devices.
The foreign body reaction results from an inflammatory reaction to the implanted medical device which initiates a cascade of cellular events, culminating in the formation of a fibrous capsule which isolates the medical device from the vascular system in the tissue. The lack of vascular communication leads to the tissue attempting to eliminate the implanted medical device by encapsulation. This reaction eventually destroys the utility of the implant.
It is known that macrophages play a central role in the foreign body reaction by initiating a cascade of cellular activity that culminates in either a state of chronic inflammation or complete encapsulation of the implanted device. An early indicator of this reaction is the appearance of fused cells known as giant cells, which are multinucleate syncytia formed by the fusion of macrophages that have been directed towards an inflammatory site. The giant cells initiate a pleiotropic pathway leading to the surrounding tissue forming a fibrous capsule, composed primarily of fibroblasts and collagen, which isolates the implanted material from the blood supply.
The present invention provides medical devices, and methods for their manufacture, that elicit a reduced foreign body reaction, or do not elicit any foreign body reaction, when implanted into an animal body.